Endocrinology Flashcards
Hypothalamic-pituitary-thyroid axis and thyroid hormone synthesis
(Review)
Weight of thyroid gland
15 to 25 grams
Composition of lobules
20-40 follicles separated by highly vascular connective tissue
Surrounds a closed cavity containing colloid, thyroid hormone, thyroglobulin, and a variety of glycoproteins
Follicular cells
Responsible for the synthesis and secretion of calcitonin, a hormone important in calcium metabolism
Parafollicular cells or C cells
Hormone stimulated by hypothalamus
TRH
Responsible for release of TSH
Anterior pituitary gland
Thyroid hormone synthesis
1 Active transport of inorganic iodide into the cell (follicular cell)
2 Iodination of the tyrosyl residues on Thyroglobulin (Tg)
3 Coupling of iodotyrosine molecules within Tg to form T4 and T3 (two separate oxidative reactions, both catalyzed by thyroid peroxidase, TPO)
T3 (1 DIT, 1 MIT)
T4 (2 DIT)
4 Proteolysis of Tg with release of free iodotyrosine, T4, and T3, and secretion of iodothyronine into the circulation
5 Deiodination of iodotyrosines within the thyroid and reuse of liberated iodide
6 Back to 1
7 Release of thyroid hormones
Thyroidal origin:
T4
T3
100%
20%
T3: 80%
Produced enzymatically in nonthyroidal tissues by 5’-monodeiodination of T4
T4
1 Thyroxine-binding globulin (TBG): 70%
2 Transthyretin: 20%
3 Albumin: 10%
Other term for transthyretin
Binding prealbumin
Free thyroid hormones
Metabolically active
T or F. Most of the circulating T3 is bound to TBG with a 10-fold reduced affinity as compared with that of T4
T
Third major form of circulating hormone
rT3
Reverse T3: Characteristics
1 No biological activity
2 Short half-life of 4 hours
3 Circulates bound to TBG
4 Its formation is considered a disposal pathway in the peripheral metabolism of T4
40% undergoes deiodination of the inner ring of T4 to form rT3
Monoiodinated T4
Influenced by intake of iodine
MIT/DIT Ratio
Preferential iodotyrosine formed
DIT
Predominant form of hormone synthesized and secreted when iodide is abundant
T4
Produced in greater quantities when iodide sources are diminished
MIT
Result of MIT production in great quantities
Increased T3 formation and release
Most common clinical syndrome caused by circulating antibodies to the TSH receptor
Graves’ disease
Signs and symptoms of hyperthyroidism
Heat intolerance, tachycardia, weight loss, weakness, emotional lability, tremor, diarrhea
Opposite of myxedema
Thyroid storm
Myxedema coma
Advanced stage of thyroid hormone deficiency characterized by progressive stupor, hypothermia, and hypoventilation
Hypothyroidism signs and symptoms
Hoarseness, cold sensitivity, dry skin, constipation, bradycardia, muscle weakness
Hypothyroidism that involves the thyroid gland
Primary
Hypothyroidism that involves the pituitary gland
Secondary
Hypothyroidism that involves the hypothalamus
Tertiary
Secondary hypothyroidism
TSH secretion is decreased as a result of a pituitary disorder
Tertiary hypothyroidism
Hypothalamic dysfunction
Causes of primary hypothyroidism
1 Ablation with radioactive iodine
2 Surgery to treat hyperthyroidism
Primary hypothyroidism
Most commonly iatrogenic in origin where there is failure to secrete thyroid hormones
Examples of euthyroidism
1 Goiter
2 Thyroid adenoma
3 Thyroid carcinoma
Permit the diagnosis of subclinical hyperthyroidism and hypothyroidism
Accurate TSH assays
History: tremors, profuse sweating, nodule in the thyroid gland
Tests of T4 and T3: normal
TSH suppressed; T4 and T3 overproduced
Euthyroidism
Other term for T3
3,5,3-triiodothyronine
Other term for T4
Thyroxine
T or F. 80% of circulating T3 comes from the peripheral deiodination of T4
T
Production rate, nmol/day
T4
T3
110
50
Fraction of circulating hormone of thyroid origin
T4
T3
100%
20%
Fraction of total hormone in free form
T4
T3
- 0002
0. 003
Half life, days
T4
T3
~7
0.75
Relative metabolic potency
T4
T3
- 3
1. 0
Serum concentration, Total, nmol/L
T4
T3
100
1.8
Serum concentration, Free, pmol/L
T4
T3
20
5
Divide by 12.87
Conversion of
1 Total T4 from nmol/L to mcg/dL
2 Free T4 from pmol/L to ng/dL
Multiply by 65.1
Conversion of
1 Total T3 from nmol/L to ng/dL
2 Free T3 from pmol/L to pg/dL
Provides an accurate diagnostic measurement
Most of ingested iodine excreted in urine
Used mainly to assess dietary intake of populations
Urinary iodine measurement
Degree of deficiency: none
Urinary iodine excretion, mcg/L: > 100
Degree of deficiency: none
Goiter prevalence: <5%
Degree of deficiency: mild
Goiter prevalence: 5%-19.9%
Degree of deficiency: mild
Urinary iodine excretion, mcg/L: 50-99
Degree of deficiency: moderate
Goiter prevalence: 2%-29.9%
Degree of deficiency: moderate
Urinary iodine excretion, mcg/L: 20-49
Degree of deficiency: severe
Goiter prevalence: >30%
Degree of deficiency: severe
Urinary iodine excretion, mcg/L: <20
Specimens for neonatal hypothyroidism
1 Dry blood spots
2 Cord serum
Measured for neonatal hypothyroidism
T4
TSH
Most sensitive test for the diagnosis of congenital hypothyroidism
Elevated TSH
Cause of false-positive results for neonatal hypothyroidism
Low T4 levels (occur in both premature infants and those with congenital absence of TBG)
It carries a high false-positive rate for neonatal hypothyroidism
Measurement of only T4
Increases during pregnancy which elevates the TBG concentration and results in an increase in the total T4 and T3 reference range to approximately 1.5 times the nonpregnancy upper reference level by 16 weeks gestation
Estrogen production
Gestational transient thyrotoxicosis
Syndrome when the increase in FT4 reaches supranormal levels and is prolonged
Serum HCG as a physiologic variable
1 Increase in T3 and FT4: fertility
2 Fall in serum TSH: first trimester
Causes an increase in total T4 and total T3
Estrogen
Suppresses TSH
Dopamine
Propanolol
Suppresses conversion of T4 to T3
Amiodarone
Causes both hypothyroidism and hyperthyroidism
First test to be requested for thyroid disorders
TSH
Best achieved by immunoassay of plasma and serum samples, such as enzyme immunoassay or fluorescent immunoassay
Analysis of thyroxine
Test for total thyroxine
EMIT
EMIT: Added to the patient sample along with enzyme-labeled thyroxine (labeled with glucose-6-phosphate dehydrogenase)
Antibody that has specificity to thyroxine
EMIT: Inhibits the enzyme activity by interfering with the enzyme’s active site for the substrate
Binding of the antibody to the enzyme-labeled thyroxine
EMIT: Wavelength
340 nm
EMIT: Directly proportional to the concentration of thyroxine in the patient sample
Rate of product formation
EMIT: Catalyzes substrate (glucose-6-phosphate dehydrogenase) to form product and NADH
Leftover unbound enzyme-labeled thyroxine
T or F. If the patient sample contains a low amount of thyroxine, there will be a low amount of leftover enzyme-labeled thyroxine to react with the substrate and form the product. When there is low concentration of patient hormone, the majority of the antibody has been bound with the enzyme-labeled thyroxine.
T
Thyroxine reference range: T4 total
Adult female
Adult male
- 5-11.0 mcg/dl
4. 6-10.5 mcg/dl
EMIT: Specimen
1 Serum
2 Dried whole blood but heparinized
3 EDTA plasma